Our studies on tumor immunity in vitro and in vivo led to the observation that macrophages capable of suppressing growth factor dependent lymphocyte responses were generated in vivo in tumor bearing animal and in vitro in unstimulated or syngeneic tumor stimulated cultures of spleen cells. The suppressors are generated in several stages involving induction, radiosensitive proliferation, and radio resistant maturation (53). Recent studies have demonstrated that interleukins of the helper system display an inhibitory effect on the generation of the suppressors. This raises the possibility that the immunosuppressed state of tumor bearing animals, at least in the context of nonspecific hyporesponsiveness, may be reversible. Our studies on the generation of the suppressor macrophages are directed towards the hypothesis that an uncommited pool of precursor monocytes can be directed toward differentiation into helper ot suppressor macrophages by the appropriate lymphocyte-derived macrophage differentiation factor. This proposes that the helper factors may have an inhibitory effect on suppressor generation initially by competing for available monocyte precursors. The specific aim of this proposal is to test this hypothesis first by determining if suppressor macrophage generation involves the induction of lymphocytes producing a factor which drives the differentiation of suppressor macrophages and second by determining if that differentiation can be diverted into generation of helper macrophages by provision of TCGF-CM.